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Randomized placebo-controlled, double-blind trial of ketanserin in claudicants. Changes in claudication distance and ankle systolic pressure. PACK Claudication Substudy.

The effect of ketanserin on intermittent claudication (measured by treadmill walking distance and ankle systolic pressure) was assessed in 594 patients, a subset of the 3,899 patients who composed a double-blind study of the effect of ketanserin on cardiovascular events. Complete data sets at the beginning and end of 1 year's treatment with ketanserin or placebo were available in 436 patients. There was no difference between the groups in the improvement in pain-free treadmill walking distance. The placebo effect on treadmill walking distance increased continuously for at least 1 year at the rate of about 15% every 6 months. There was no significant change in either group in the ankle systolic pressure at the end of the treatment period but in the group given ketanserin, brachial systolic pressure was decreased and the ankle to arm systolic pressure ratio therefore increased. There was only a very weak association between treadmill walking distance and ankle to arm systolic pressure ratio both at the beginning and in terms of change over 1 year. Therefore, this pressure ratio is probably not a useful way of assessing the effects of medical treatment of claudication.

Blood Pressure↗

Epidemiology of peripheral arterial disease.

With the aging of the population of most developing nations, arteriosclerosis is becoming a major health problem. Although much research has concentrated on the coronary and cerebral forms of the disease, peripheral arterial disease has received little attention from epidemiologists. The "Rose questionnaire" has been used extensively to diagnose intermittent claudication; however, the current method of choice for the diagnosis of peripheral arterial disease in epidemiologic studies is the ankle brachial pressure index. The prevalence of intermittent claudication, diagnosed by the Rose questionnaire, differs according to age, sex, and geographical location varying between 0.4 and 14.4%; similar variability (from 4.2 to 35%) is seen for disease diagnosed by the ankle brachial pressure index. The major risk factor for peripheral arterial disease is cigarette smoking; hypertension and diabetes have been identified as risk factors in a number of studies; impaired glucose metabolism, dislipidemia, degree of physical activity, and coagulation factors have been identified in some populations. The coexistence of cardiocerebrovascular and peripheral vascular diseases enhances the risk of early death, which is more than double that in the general population: The most frequent cause of death is myocardial infarction. More work is required to document the natural history of the disease, the risk factors for its progression, its relationship with cardiovascular disease, and the effect of intervention strategies.

Age Factors↗

The complication rate of percutaneous peripheral balloon angioplasty.

One thousand six hundred and forty-two vessel segments (46% iliac, 54% femoro-distal) in 1141 patients have undergone percutaneous peripheral balloon dilatation at the Northern General Hospital, Sheffield over a 9 year period. Forty-two significant complications were encountered in all; 28 of these were occlusive and half of these were treated by angioplasty itself, either by thrombolysis or catheter suction. There was one case of distal ischaemia attributed to cholesterol embolisation which led to death (Gaines et al., 1988). There were two cases of perforation and haematoma requiring surgery, one retroperitoneal haemorrhage and one false aneurysm. One diabetic patient developed septicaemia following successful PTA for an ischaemic foot and died. One case each of bowel ischaemia, cerebrovascular accident and myocardial infarction occurred within 24 h of the angioplasty procedure, but there was no clear causal relationship. Arterial wall dissection or perforation per se was not considered a complication unless it progressed to haemorrhage or vessel occlusion. There were three cases of femoral nerve damage causing sensory loss in the thigh, two of which were permanent. Four hundred and thirty-five procedures were performed in patients with rest ischaemia. Of these, 2.8% developed complications requiring surgery, but only 0.9% required reconstructive bypass surgery. For intermittent claudication 1207 procedures were performed, 0.7% of these developed complications requiring surgery but only 0.5% required reconstructive surgery. These results justify the use of angioplasty in the treatment of intermittent claudication and in poor risk patients with threatened limb loss.

Angioplasty, Balloon↗

Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This chapter about antithrombotic therapy for peripheral arterial occlusive disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients with chronic limb ischemia, we recommend lifelong aspirin therapy in comparison to no antiplatelet therapy in patients with clinically manifest coronary or cerebrovascular disease (Grade 1A) and in those without clinically manifest coronary or cerebrovascular disease (Grade 1C+). We recommend clopidogrel over no antiplatelet therapy (Grade 1C+) but suggest that aspirin be used instead of clopidogrel (Grade 2A). For patients with disabling intermittent claudication who do not respond to conservative measures and who are not candidates for surgical or catheter-based intervention, we suggest cilostazol (Grade 2A). We suggest that clinicians not use cilostazol in patients with less-disabling claudication (Grade 2A). In these patients, we recommend against the use of pentoxifylline (Grade 1B). We suggest clinicians not use prostaglandins (Grade 2B). In patients with intermittent claudication, we recommend against the use of anticoagulants (Grade 1A). In patients with acute arterial emboli or thrombosis, we recommend treatment with immediate systemic anticoagulation with unfractionated heparin (UFH) [Grade 1C]. We also recommend systemic anticoagulation with UFH followed by long-term vitamin K antagonist (VKA) in patients with embolism [Grade 1C]). For patients undergoing major vascular reconstructive procedures, we recommend UFH at the time of application of vascular cross-clamps (Grade 1A). In patients undergoing prosthetic infrainguinal bypass, we recommend aspirin (Grade 1A). In patients undergoing infrainguinal femoropopliteal or distal vein bypass, we suggest that clinicians do not routinely use a VKA (Grade 2A). For routine patients undergoing infrainguinal bypass without special risk factors for occlusion, we recommend against VKA plus aspirin (Grade 1A). For those at high risk of bypass occlusion and limb loss, we suggest VKA plus aspirin (Grade 2B). In patients undergoing carotid endarterectomy, we recommend aspirin preoperatively and continued indefinitely (Grade 1A). In nonoperative patients with asymptomatic or recurrent carotid stenosis, we recommend lifelong aspirin (Grade 1C+). For all patients undergoing extremity balloon angioplasty, we recommend long-term aspirin (Grade 1C+).

Arterial Occlusive Diseases↗

Steroid sex hormones for lower limb atherosclerosis.

BACKGROUND: There is accumulating evidence that steroid sex hormones have a beneficial effect on a number of risk factors for peripheral arterial disease. OBJECTIVES: The objective of this review was to determine whether exogenous steroid sex hormones are an effective treatment for patients with lower limb atherosclerosis. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group trials register was searched, together with reference lists from relevant articles and reviews obtained through searches of Embase and Medline. SELECTION CRITERIA: Randomised controlled trials of steroid sex hormones in patients with lower limb atherosclerosis were selected. DATA COLLECTION AND ANALYSIS: Both reviewers extracted data and assessed trial quality independently. Whenever possible investigators were contacted to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: Four trials appeared to meet the inclusion criteria, but one was excluded because of poor methodology and another is awaiting translation into English. The two remaining trials compared testosterone treatment with placebo in a total of 83 men with intermittent claudication. No trials were available which investigated the potentially beneficial effects of oestrogenic hormones in women with lower limb atherosclerosis. Testosterone therapy produced no improvement in tests of walking distance or in a variety of other objective tests for peripheral arterial disease, including venous filling time, muscle blood flow and plethysmography. The odds ratio for subjective improvement in symptoms using the combined trial results was also non-significant (odds ratio 1.28, 95% confidence interval 0.61 to 2.65). REVIEWER'S CONCLUSIONS: There is no evidence to date that short-term testosterone treatment is beneficial in male subjects with lower limb atherosclerosis. However, this might reflect limited data rather than the lack of a real effect.

Arteriosclerosis↗

Cauda equina pseudoclaudication syndrome.

Intermittent claudication is known as a specific symptom in patients with chronic occlusive arterial lesions. Clinically it is important that neurogenic intermittent pseudo-claudication should be differentiated from true intermittent claudication. Nevertheless confusion still exists in differential diagnosis between these two entities. This paper deals with general review of intermittent pseudo-claudication and a particular emphasis is placed on the different concepts of the pathophysiology and the differential diagnosis from the standpoint of vascular surgery. Recently one case of the neurogenic intermittent pseudo-claudication was encountered and presented in this paper.

Cauda Equina↗

Femoropopliteal bypass using polytetrafluoroethylene.

Reinforced expanded polytetrafluoroethylene (PTFE) was used as a femoropopliteal bypass graft in 31 patients (37 operations). The indications were intermittent claudication (13 operations), severe ischaemia with rest pain or gangrene (20 operations), and prophylactic treatment of popliteal aneurysms (4 operations). The one-year accumulative patency rates were 75% for patients with intermittent claudication and 20% for patients with severe ischaemia. In three patients with claudication, graft thrombosis led to amputation in spite of attempted graft thrombectomy. These results compare unfavourably with our experience using autogenous vein, in which the one-year accumulative patency rates were 80% for claudication and 70% for severe ischaemia, and in which failure of the bypass graft for claudication rarely made the patient worse.

Aged↗

[Clinical assessment of treatment results for atherosclerotic ischemia of the lower extremities with intraarterial ozone injections].

Ten injections of O3 into femoral arteries were administered to 50 patients with atherosclerotic ischemia of the lower extremities and to 49 diabetic patients. All patients were assessed clinically with the ankle-arm index, measurement of intermittent claudication distance prior to and after the treatment. The treatment showed a significant improvement in both groups manifested by an increase in ankle-arm index, and prolongation of the intermittent claudication distance by more than twice. The treatment of atherosclerotic ischemia of the lower extremities with O3 is both valuable and safe.

Arteriosclerosis↗

[Circadian variations of cutaneous blood flow in normal subjects and in patients with peripheral arteriopathies. Effect of PGE1 and alpha-cyclodextrin].

BACKGROUND: In this study the circadian skin flux pattern was evaluated in 10 normal reference subjects and in 35 patients (mean age 68 +/- 11) subdivided in groups (10 with intermittent claudication (200-400 m of walking distance), 10 diabetics with claudication, 7 patients with rest pain and 8 with localised gangrene). METHODS: A laser Doppler flowmeter was used to monitor skin flux for 24 hours. In patients with intermittent claudication the circadian pattern was comparable to normal subjects. In diabetics the daily curve showed several irregular peaks mostly dissociated from activity or rest. RESULTS: In patients with critical ischaemia severe alterations of the circadian pattern were observed (the daily curve was flattened and dissociated from activity or rest) particularly in gangrene. PGE1 alpha-ciclodestrina treatment (60 micrograms/day) partially restored the circadian pattern and increased the average values of the 24-hour curve. In rest pain and gangrene the infusion of PGE1 alpha-ciclodestrina in the late evening increased the average night flux (which tended to fall to very low levels causing pain) and prevented or abolished night rest pain.

Alprostadil↗

The relationship between free-living daily physical activity and the severity of peripheral arterial occlusive disease.

The purposes of this study were to assess the magnitude of the reduction in free-living daily physical activity of claudicants compared with age-matched controls, and to examine the relationship between the severity of peripheral arterial occlusive disease (PAOD) and free-living daily physical activity. Eighty-five PAOD patients with intermittent claudication and 59 non-PAOD subjects with a resting ankle/brachial index (ABI) of 0.63 +/- 0.20 and 1.21 +/- 0.08, respectively, were monitored for 2 consecutive weekdays with an accelerometer and pedometer worn on each hip. The times to onset and to maximal claudication pain were also measured in the claudicants during a graded treadmill test to assess the functional limitations imposed by PAOD. The PAOD group had a 42% lower energy expenditure as measured from the accelerometer (357 +/- 238 kcal/day versus 616 +/- 363 kcal/day; p < 0.001) and a 45% lower pedometer reading (4737 +/- 2712 steps/day versus 8672 +/- 4235 steps/day; p < 0.001) than the non-PAOD group. Furthermore, the relationship between free-living daily physical activity and ABI in PAOD patients was significant for both the accelerometer (r = 0.41; p < 0.001) and the pedometer (r = 0.41; p < 0.001). The rate of decline in free-living daily activity was 42 kcal/day and 612 steps/day per 0.10 drop in ABI. The correlation between free-living daily physical activity and time to maximal claudication pain (6:25 +/- 3:30 min:s) in the PAOD group was significant for both the accelerometer (r = 0.30; p = 0.05) and the pedometer (r = 0.36; p = 0.03). However, the time to onset of claudication pain (3:02 +/- 2:22 min:s) in the PAOD group was not related to either the accelerometer (r = -0.02; p = 0.86) or the pedometer (r = 0.18; p = 0.28) activity values. In conclusion, free-living daily physical activity was 42% to 45% lower in PAOD patients with intermittent claudication than in apparently healthy subjects of similar age. Moreover, claudicants were progressively more sedentary with an increase in PAOD severity.

Adenosine Diphosphate↗

Exercise training and peripheral vascular disease.

BACKGROUND: Conservative management is advocated as a treatment of choice for patients with intermittent claudication. This is a review of the mechanisms behind the improvement following an exercise rehabilitation programme. METHODS: All Medline articles from the National Library of Medicine, USA containing the text words 'claudication' or 'peripheral vascular disease' and 'exercise' were reviewed. Cross-referencing from relevant articles was carried out. RESULTS AND CONCLUSION: The poor physical status of a patient with intermittent claudication is not solely due to a reduction in blood flow to the lower limbs; associated factors, such as metabolic inefficiency, poor cardiorespiratory reserve and exercise-induced inflammation contribute. An exercise programme frequently improves both the physical aspect and quality of life, and the success of such exercise is multifactorial. An increase in the blood flow to the lower extremity is uncommon. Other factors, such as a redistribution of blood flow, changes in oxidative capacity of the skeletal muscles and greater utilization of oxygen, occur and the associated metabolic dysfunction of the skeletal muscles is rectified. Following exercise training, blood rheology improves and exercise-induced inflammation is ameliorated; cardiorespiratory status also benefits and the oxygen cost of exercise decreases.

Biomechanical Phenomena↗

Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease.

BACKGROUND: To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication. METHOD: Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training. RESULTS: Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group. CONCLUSION: These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.

Aged↗

The PADHOC device is a better guide to the actual incapacity suffered by claudicants than the gold standard constant load treadmill test.

BACKGROUND: The Constant Load Treadmill Test (CLTT) is currently the primary method used to measure walking impairment in patients with peripheral vascular disease. The aim of this study was to compare the CLTT and PADHOC device as assessments of walking impairment. METHODS: 55 patients with intermittent claudication underwent a CLTT and a Double Physiological Walking Test (DPWT) using the PADHOC device. Health-related quality of life was measured using the Short Form 36 and the Claudication Scale. RESULTS: The initial claudication and maximum walking distance from the first part of the DPWT showed the best correlation with domains of pain and physical function. CONCLUSIONS: The DPWT is more representative of the functional incapacity experienced by patients with intermittent claudication. We believe that the PADHOC is a suitable alternative to the CLTT in the assessment of this patient group.

Aged↗

Popliteal artery entrapment syndrome: accurate morphological diagnosis utilizing MRI.

A case of bilateral popliteal artery entrapment syndrome was accurately diagnosed utilizing magnetic resonance imaging (MRI) in a 34-year-old male with intermittent claudication. The abnormal structure was clearly visualized in relation to the popliteal artery in T1-weighted sagittal and axial sections of MRI. The type of entrapment was determined by this method prior to surgery. Intermittent claudication disappeared after surgical repair. Our experience emphasizes that MRI facilitates the accurate morphological diagnosis of popliteal artery entrapment syndrome.

Adult↗

Characteristics of the limb circulation in hypertension.

The aim of this study was to investigate the effect of hypertension on the regulation of limb circulation. The study group consisted of 50 patients suffering from hypertension; in 21 cases the peripheral circulation was intact, while 29 patients had peripheral obliterative arterial disease (POAD) (clinical symptoms: intermittent claudication or rest pain). The control group consisted of 67 normotensive patients. In 33 subjects of the control group the peripheral circulation was intact, while 34 patients suffered from POAD (clinical symptoms: intermittent claudication or rest pain). The total limb blood flow (LBF) was measured by using venous isotope dilution technique. In hypertensive patients the limb vascular resistance (LVR) was markedly elevated, but the LBF remained in the normal range. In patients suffering from both hypertension and POAD the LVR was pathologically elevated and the LBF markedly diminished. After acute vasodilator therapy the LBF significantly increased, despite the drop in blood pressure owing to the extensive decrease of the LVR. It appears that in hypertension the elevation of the LVR is the most characteristic change of the limb circulation. The elevation of the arterial blood pressure has no favorable effect on the limb circulation, and the LBF compared with the blood pressure is relatively low.

Adolescent↗

The peripheral circulation and treatment of hyperlipoproteinemias.

Forty patients with hyperlipoproteinemia were followed 4-9.3 years by non-invasive tests of their lower extremity circulation. Twenty-eight patients were treated by diet and/or drugs, and 12 patients were controls. Although all patients had abnormal non-invasive tests, only 15 patients had intermittent claudication. Seven patients had improved circulation tests while 13 showed a deterioration in the tests; 20 patients had no changes. The patients who showed improvement in tests had the highest incidence of intermittent claudication and the lowest average ankle to brachial artery systolic blood pressure index. Although treatment patients had a significant decrease in total cholesterol, triglycerides, and VLDL, no significant differences were found when the results of the circulation tests were analyzed according to treatment or control status of the patients, to abnormal lipid patterns, or, ignoring treatment status, to a decrease in lipids. The patients who showed a deterioration in tests had a significantly higher total cholesterol level at the beginning of, but not during, the study and did not significantly decrease their triglycerides. No significant changes occurred in HDL, LDL, or VLDL. This study presents a methodology for the long-term, non-invasive assessment of peripheral arterial disease and a pilot study for its application. Despite the small number of patients studied, the failure to demonstrate benefit would discourage a larger clinical trial of this treatment protocol.

Adult↗

[Reduction of cardiovascular morbidity/mortality in arteriopathies treated ith PGE1 alpha-cyclodextrin].

BACKGROUND: Cardiovascular morbidity and mortality were evaluated in two groups of vascular patients (one treated with PGE1 alpha-ciclodestrina according to the short term protocol and one reference group) with a follow up of at least 24 month. METHODS: The former group included patients who had been treated with at least four PGE1 alpha-ciclodestrina, short-term treatment cycles per year while the latter was a historical reference group managed without prostaglandins. The two groups were comparable for sex and age distribution. RESULTS: In the PGE1 alpha-ciclodestrina group 142 patients (mean age 64 +/- 17; M:F = 84:58) had been treated (47 for intermittent claudication and 95 for critical ischemia: 43 for rest pain, and 52 for localised gangrene). The historical reference group included 157 patients (mean age 65 +/- 18: M:F = 91:66); 53 with intermittent claudication and 104 with critical ischemia (49 rest pain, 55 gangrene). In claudicants yearly cardiovascular morbidity was reduced from the 15% observed in the reference group to 10% in patients treated with PGE1 alpha-ciclodestrina. Yearly mortality decreased from 11% in the reference group to 6% in the treated group. In rest pain patients morbidity decreased from 24% in the reference group to 19% in the treated group. Mortality also decreased (from 16% to 11%). In patients with gangrene the difference in morbidity between the reference group (35%) and the PGE1 alpha-ciclodestrina group (27%) was even more evident (P < 0.025). In this group the mortality per year was reduced from 26% in the reference group to 17% in the PGE1 alpha-ciclodestrina treated group. CONCLUSION: It appears that cyclic treatment with PGE1 alpha-ciclodestrina produces not only an improvement in signs and symptoms related to vascular disease but also an important decrease in cardiovascular morbidity and mortality which has not been previously reported.

Age Distribution↗

HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study.

OBJECTIVE: To assess the relation between HbA(1c) (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS: This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9). RESULTS: During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94-2.87], P trend = 0.08). CONCLUSIONS: We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD.

Cohort Studies↗